Effects of hormonal replacement therapy in postmenopausal hypertensive patients.

OBJECTIVE: To evaluate the effect of hormonal replacement therapy (HRT) on blood pressure (BP) in postmenopausal hypertensive women. METHODS: Sixty women affected by hypertension were enrolled and randomized in two groups of treatment: transdermal continuous HRT in a sequential regimen (group A) and placebo (group P). At baseline, after 3 and 6 months of treatment, the BP with standard sphygmomanometer and with 24-h ambulatory recording method was evaluated in two periods (from day 10 through day 16 of the cycle and from day 20 through day 27 of the cycle). At the same time, we also evaluated total cholesterol, LDL-c, HDL-c, triglycerides, and fibrinogen levels. RESULTS: After 3 and 6 months of treatment, no significant variations of systolic and diastolic BP measured with standard sphygmomanometer were detected in both groups. On the contrary, in group A in comparison with basal values and group P, and without difference between the two phases of treatment, the 24-h recording showed a significant (P<0.05) decrease in BP. No significant variations were detected in group P versus baseline. In particular, we observed in group A at 3 months of treatment a significant (P<0.05) decrease only in daytime BP in comparison with basal values and group P, without difference between the two phases of treatment. Indeed, the decrease in daytime BP was significant (P<0.05) for both systolic and diastolic BP. At 3 and 6 months a significant (P<0.05) decrease in total cholesterol, LDL-c and fibrinogen levels was detected in group A versus baseline and group P. HDL-c and triglyceride concentrations showed no significant variations. CONCLUSIONS: The transdermal HRT induces a significant reduction of BP values and a favorable metabolic action in postmenopausal hypertensive patients.

Ultrasonographic endometrial monitoring during continuous-sequential hormonal replacement therapy regimen in postmenopausal women.

OBJECTIVE: To evaluate the endometrial thickness in different periods of a continuous-sequential HRT regimen and to correlate the ultrasonographic findings with the histological patterns. METHODS: The study was structured in two phases. In the 1st phase, 37 postmenopausal women (group A) treated by at least 6 months with a conventional continuous-sequential hormonal replacement therapy (cs-HRT) regimen were enrolled. In all patients, the endometrial thickness was measured at the 7th, 14th, 21st and 25th day of the cycle using transvaginal ultrasonography (TV-USG). In the 2nd phase of the study, other 41 postmenopausal women (group B) were enrolled and treated with the same sc-HRT regimen. At entry and after six cycles of cs-HRT, an endometrial biopsy was performed. The endometrial pattern was related with endometrial thickness. Either the evaluations were performed immediately after progestogen withdrawal bleeding, as showed by 1st phase results. RESULTS: The results of the 1st phase of the study showed a mean endometrial thickness significantly lower at 7th day of the cycle compared to 14th, 21st and 25th day (4.3+/-1.2 versus 6.6+/-2.9, 7.8+/-4.2 and 7.4+/-4.6 mm+/-SD, respectively). After six cycles of cs-HRT (2nd phase of the study), the mean endometrial thickness was significantly increased in comparison with basal values (4.2+/-1.5 versus 2.8+/-1.2 mm+/-SD; P<0.05). Endometrial biopsies showed 13 cases (39.4%) of atrophy and 20 cases (60.6%) of proliferative endometrium. Mean endometrial thickness in case of atrophy was lower than in presence of a proliferative endometrium (3.7+/-1.2 versus 4.4+/-1.4 mm+/-SD; not significant). Endometrial thickness was <4 mm in 16 cases (11 of atrophic and five of proliferative endometrium), between 4 and 5 mm in 15 cases (13 of proliferative and two of atrophic endometrium) and between 5 and 6 mm in two cases (either case of proliferative endometrium). CONCLUSIONS: The best timing for monitoring endometrial thickness during cs-HRT regimens is the period immediately after withdrawal bleeding improving the reliability of the ultrasonographic exam to identify endometrial pathologies.

Effects of raloxifene treatment on uterine leiomyomas in postmenopausal women.

OBJECTIVE: To evaluate the effects of raloxifene administration on uterine and uterine leiomyoma sizes in postmenopausal women. DESIGN: Prospective randomized, double-blind, placebo-controlled clinical trial. SETTING: Department of Gynecology, Obstetrics, and Pathophysiology of Human Reproduction, University of Naples "Federico II", Italy. PATIENT(S): Seventy spontaneous postmenopausal women affected by uterine leiomyomas. INTERVENTION(S): Twelve cycles (of 28 days each) of treatment with raloxifene (60 mg daily per os) or placebo. MAIN OUTCOME MEASURE(S): At entry and at every 3 cycles, uterine and uterine leiomyoma dimensions were measured by means of transvaginal ultrasound. The difference between uterine and leiomyoma volumes (Delta size) was calculated in all subjects. The characteristics of uterine bleeding and the side effects of the treatments were assessed using a daily diary. RESULT(S): After 6, 9, and 12 cycles of therapy, in subjects treated with raloxifene, the mean uterine and uterine leiomyoma size were significantly decreased, and the mean Delta size significantly increased in comparison with basal values and the placebo group. No significant differences in uterine bleeding were detected between the two groups. CONCLUSION(S): In postmenopausal women raloxifene appears to act selectively on uterine leiomyomas, reducing their size.

Effectiveness of short-term administration of tibolone plus gonadotropin-releasing hormone analogue on the surgical outcome of laparoscopic myomectomy.

OBJECTIVE: To evaluate whether administration of tibolone changes the effectiveness of GnRH analogue administered before laparoscopic myomectomy. DESIGN: Prospective, randomized, open, placebo-controlled clinical trial. SETTING: Department of Gynecology and Obstetrics, University of Naples Federico II, Naples, Italy. PATIENT(S): 66 women with symptomatic uterine leiomyomas. INTERVENTION(S): Treatment for 2 months with leuprolide acetate and iron tablets, plus tibolone (group A) or placebo tablets (group B); or with leuprolide acetate and iron tablets (group C). MAIN OUTCOME MEASURE(S): Laparoscopic myomectomy at the end of treatment. Operative time and blood loss during surgery were recorded. Uterine volume, volume and number of uterine leiomyomas, volume and echogenicity of the largest uterine leiomyomas, hematologic data, and myoma-related symptoms were evaluated at baseline and 1 week before and after surgery. RESULT(S): Uterine and leiomyomata volume and myoma-related symptoms were significantly reduced and hematologic variables improved significantly in groups A and B, compared with baseline values and with group C. Operative time and blood loss were significantly less in groups A and B than in group C. After surgery, hematologic variables were significantly worse in group C compared with groups A and B. During the study no significant difference was detected between groups A and B. CONCLUSIONS: Administration of tibolone administration in patients treated with GnRH analogue before laparoscopic myomectomy does not change the effectiveness of the analogue administered alone.

[Effect of combined conjugated estrogen-medrogestone replacement therapy on lipid profiles, climacteric symptoms and the endometrium]. / Effets sur les lipides, les symptômes climatériques et l'endomètre d'une association d'estrogènes conjugués et de médrogestone dans le traitement hormonal substitutif.

OBJECTIVE: To assess the effects of continuous administration of conjugated estrogen combined with sequential administration of medrogestone on lipid profiles, climateric symptoms and endometrial tolerance. METHODS: This multicenter open study was conducted for one year to assess the effects of a hormone replacement therapy (HRT) regimen using Premarin (0.625 mg/day 28d/28) combined with medrogestone 5mg for 12 days (d17-d28 of each 28-day cycle) on lipid profiles, climateric symptoms and cycle control in 228 post menopausal women with an intact uterus. The subjects were recruited in 23 centers in 7 countries in Europe and Asia. Serum lipid/lipoprotein levels were determined at baseline and at cycles 3, 6, 13; endometrium biopsies were performed at screening then at cycle 13. Climateric symptoms and bleeding patterns were recorded by the patients from daily diaries cards collected at baseline and at visits during cycle 3, 6, 9, and 13. RESULTS: By cycle 3, the conjugated estrogen-medrogestone combination induced significant modifications of the lipid profile which were judged favorable. These modifications were maintained throughout treatment. All the baseline values were within normal limits. Mean variations compared with baseline values (expressed in mmol/l) after cycles 3, 6, and 13 were -0.46, -0.54, and -0.46 for total cholesterol (p<0.05), + 0.053, + 0.057, and + 0.078 for HDL-cholesterol (p<0.05) and -0.556, -0. 542, and -0.493 for LDL-cholesterol (p<0.001) respectively. VLDL-cholesterol levels were unchanged. Triglycerides increased significantly though moderately: + 0.12, + 0.15, and + 0.15 mmol/l at cycles 3, 6, and 13 respectively. Endometrial biopsies obtained at cycle 13 (n=195) did not reveal any endometrial hyperplasia. Withdrowal bleeding was predictable for a 6 to 7.4 day interval. The incidence of irregular bleeding varied from 7 to 33% and decreased progressively over the 13-cycle treatment. The incidence of amenorrhea increased from 14 to 52% over the 12 months studied. Finally, at each cycle, menopausal symptoms (mean number of hot flushes/day and Küpperman score) were significantly improved compared with the baseline. As expected, modifications were more pronounced after cycle 1, but improvements were maintained throughout the study. CONCLUSION: Continuous administration of Premarin in combination with sequential administration of medrogestone was found to be an effective treatment for menopausal symptoms. It was associated with favorable modifications of the lipid profile and was safe for the endometrium.

Long-term administration of tibolone plus gonadotropin-releasing hormone agonist for the treatment of uterine leiomyomas: effectiveness and effects on vasomotor symptoms, bone mass, and lipid profiles.

OBJECTIVE: To evaluate the effects of long-term administration of GnRH agonist (GnRH-a) plus tibolone for uterine leiomyomatosis. DESIGN: Prospective open clinical trial. SETTING: Department of Gynecology, Obstetrics and Pathophysiology of Human Reproduction, University of Naples "Federico II", Naples, Italy. PATIENT(S): Twenty-five subjects with symptomatic uterine leiomyomas. INTERVENTION(S): Treatment for 2 years with leuprolide acetate (3.75 mg IM every 28 days) and tibolone (2.5 mg/d per os). MAIN OUTCOME MEASURE(S): Uterine and uterine leiomyoma sizes, endometrial thickness, lumbar spine bone mineral density (BMD), bone metabolism, lipid profile, myoma-related symptoms at baseline and every 6 months. Hot flashes and vaginal bleeding episodes recorded in a daily symptom diary. RESULT(S): After 6 months of treatment, a significant reduction was observed in uterine and leiomyoma volumes and myoma-related symptoms compared with baseline values. No significant change was observed in bone turnover, lumbar BMD, or serum total cholesterol, low-density lipoprotein cholesterol, or triglyceride levels. High-density lipoprotein cholesterol values were significantly lower than baseline values after 6 months of treatment but not after 18 months of therapy. A low mean number of hot flashes per day was observed. CONCLUSION(S): Long-term administration of GnRH-a plus tibolone reduces hot flashes and prevents bone loss without changing the lipid profile.

Effects of postmenopausal hypoestrogenism on skin collagen.

OBJECTIVE: The aim of our study was to evaluate the effect of aging and postmenopausal hypoestrogenism on skin collagen content. METHODS: Thirty-two women (mean age 48.78 +/- 9.86; year +/- S.D., range 28-68), 14 in premenopause and 18 in postmenopause, underwent skin biopsies performed during laparotomic operation. The amount of collagen type I, III and type III/type I ratio was evaluated by immunohistochemistry and computerised image analysis, and was related to age and years of postmenopause. RESULTS: In the postmenopausal patients, a significant (P < 0.01) decrease of percentage of skin collagen type I, type III and type III/type I ratio was observed in comparison to premenopausal women. The percentages of collagen type I, type III and type III/I ratio of all patients studied was significantly (P < 0.01) correlated with chronological age (r = 0.88, 0.89 and 0.61, respectively). Considering only postmenopausal subjects, the correlation with chronological age was significant (P < 0.01) for collagen type I and type III of postmenopausal women (r = 0.59, r = 0.64, respectively), but not for the type III/I ratio (r = 0.37, P = 0.131). The percentages of collagen type I, type III and type III/I ratio of postmenopausal women showed a significant (P < 0.01) inverse correlation with years of postmenopause (r = 0.76, 0.73 and 0.73, respectively). CONCLUSIONS: Our data suggest that the decrease of skin collagen is an estrogen-related phenomenon.

A clinical trial of the effects of tibolone administered with gonadotropin-releasing hormone analogues for the treatment of uterine leiomyomata.

OBJECTIVE: To evaluate the effects of tibolone therapy in association with GnRH-a on uterine leiomyomata, on climacteric-like symptoms, on bone metabolism, and on the lipid profile. DESIGN: A prospective, randomized, double-blind, placebo-controlled, clinical trial. SETTING: Department of Gynecology and Obstetrics, University of Naples "Federico II," Naples, Italy. PATIENT(S): Fifty women with symptomatic uterine leiomyomata. INTERVENTION(S): Six months of treatment with leuprolide acetate (3.75 mg every 28 days IM) combined with daily placebo tablets (group A) or with 2.5-mg of tibolone per os (group B). MAIN OUTCOME MEASURE(S): Uterine and uterine leiomyomata sizes, lumbar spine bone mineral density, biochemical markers of bone metabolism, lipid profile, and myoma-related symptoms were measured at baseline and after 6 months of treatment. Daily symptom diary in which hot flushes and vaginal bleeding episodes were recorded. RESULT(S): No differences between the 2 groups in uterine and uterine leiomyomata size and myoma-related symptoms were detected. After 6 months of treatment, there were statistically significant changes from baseline in bone mineral density and in biochemical markers of bone metabolism in group A but not in group B. Vasomotor symptoms were significantly lower in group B than in group A. There was a statistically significant increase (P<.01) in serum total cholesterol, high-density lipoprotein cholesterol, and triglycerides in group A after 6 months of treatment in comparison with baseline values. The difference in serum total cholesterol and triglyceride levels after 6 months of treatment in group B was not statistically significant in comparison with baseline values, but was statistically significant in comparison with group A values (P<.01). In group B, levels of high-density lipoprotein cholesterol were significantly lower after 6 months of therapy in comparison with baseline values and in comparison with group A values (P<.01). There were no statistically significant changes at baseline and after 6 months of treatment in the level of low-density lipoprotein cholesterol in either group. CONCLUSION(S): Administration of tibolone in association with GnRH-a reduces vasomotor symptoms and prevents bone loss, without compromising the therapeutic efficacy of GnRH-a alone.

Ultrasonographic measurement of endometrial thickness during hormonal replacement therapy in postmenopausal women.

The objective of this study was to measure endometrial thickness by transvaginal ultrasonography during two regimens of hormonal replacement therapy (HRT) in postmenopausal women and to compare these data with endometrial histology. Transvaginal ultrasonographic evaluation of endometrial thickness and endometrial biopsy were performed in 80 postmenopausal women before and after 6 months of HRT (between the 24th and the 28th day of the cycle). The group was randomized so that 40 women (Group A) were treated with a continuous sequential regimen consisting of 5 micrograms/day of estradiol continuously and 5 mg/day of medrogestone from the 17th to the 28th day of the cycle; and 40 women (Group B) were given continuous administration of 50 micrograms/day estradiol and 5 mg/day medrogestone. Prior to therapy, there was no significant difference in mean endometrial thickness between the groups. After 6 months of therapy, endometrial thickness was significantly increased in comparison with basal values in both groups. The mean value was significantly higher (p < 0.001) in Group A (8.5 +/- 3.7 mm) than in Group B (3.6 +/- 1.3 mm). In Group A, endometrial thickness was < or = 4 mm in 16.7% of patients and < or = 8 mm in 69.5% of patients. In Group B, 91% of patients had an endometrium of < or = 4 mm. In both groups, the thickness of the atrophic endometrium was less than that of the other histological types of endometrium (4.1 +/- 0.3 mm for Group A and 3.5 +/- 1.2 mm for Group B). In Group A, the difference in mean endometrial thickness between the proliferative and secretory endometrium was not statistically significant. In both groups, the transvaginal ultrasonographic measurement of endometrial thickness of < or = 4 mm had a high sensitivity for detecting atrophic endometrium (83.3% for Group A and 93.7% for Group B).

[Effect of hormone replacement therapy on postmenopausal ocular function]. / Effetti della terapia ormonale sostitutiva sulla funzionalità oculare in postmenopausa.

OBJECTIVE: Determination of the effects of hormonal replacement therapy (HRT) on various ocular parameters and symptoms in postmenopausal women. DESIGN: Prospective study. SETTING: Department of Obstetrics and Gynecology, University "Federico II" of Naples. PATIENTS: 14 healthy women treated orally with equine conjugated estrogen in continuous (0,625 mg/daily) and acetate-medroxyprogesteron (10 mg/daily) from 17th to 28th day for three months. MEASURES: Ocular symptomatology, intraocular pressure (IOP), lacrimal secretion, reflected and basal and corneal thickness. RESULTS: After 3 months of HRT the IOP was reduced of 10.8% (p < 0.005), the lacrimal secretion, reflected and basal, increased of 19% and 48%, respectively and the corneal thickness increased of 16.6%. CONCLUSION: The HRT has a positive effect on ocular physiology.

[Postmenopausal osteoporosis: therapeutic approaches]. / Osteoporosi postmenopausale. Approcci terapeutici.

The preventive and therapeutical measures to be implemented the post-menopausal osteoporosis are varied, although there is no clear, single protocol of intervention. ESTROGENS AND PROGESTOGENS: It si verify that the administration of estrogens and/or progestogens prevents bone loss with an action on mineral components of bone and on collagenic metabolism. BIPHOSPONATES: Operate inhibiting mineralization and, particularly, bone reabsorption. At present its use, in low dosages, is reserved to "fast bone loser" patients. CALCITONIN: It increases bone mass and significantly reduces the frequency of fractures in comparison with only calcium, but its use is limited by high costs. IPRIFLAVONE: Anti-reabsorption effects has on bone and stimulates osteoblastic activity; besides, it seems to developed the effect of estrogens on the bone. FLUORIDES: Fluorides also operate on both components of bone turnover, with a most important action on bone formation. An interesting approach is the association of low doses of monofluorophosphate with calcium. However, further confirmation of the "quality" of neoformed bone is necessary. CALCIUM: Calcium supplementation is obligatory where the alimentary supply of calcium is lower then 1 g/die or where an osteomalacic component coexists; only dosages higher than 15 g/die can produce/pharmacological effects on bone turnover. CALCITRIOL: The use is still disputed. The calcitriol-calcium association seems convincing haveved. ORG: OD 14. The efficacy of this synthetic steroid to prevent bone loss is probably superimposable on the efficacy of classic estrogen therapy.

Effects of thyroxine therapy on bone metabolism in postmenopausal women with hypothyroidism.

OBJECTIVE: To evaluate whether thyroid stimulating hormone-suppressive thyroxine replacement therapy increases bone loss in postmenopausal women. MATERIALS AND METHOD: The study had a cross-sectional design. Fifty-four postmenopausal women on long-term treatment with thyroxine for primary hypothyroidism, who showed suppressed thyroid stimulating hormone levels were enrolled in our study. In these patients and in a control group of 54 healthy postmenopausal women we evaluated bone mineral density at distal radius and the main biochemical parameters of bone turnover. Student's t test, Wilcoxon signed rank-test, Chi-square test and the univariate linear regression in the statistical analysis of the data were employed. RESULTS: Bone mineral density values, expressed as z-scores, in the treated group were significantly decreased in comparison with the control group (p < 0.01). We did not detect a significant relationship between different L-thyroxine doses administered and bone mineral density z-scores. On the contrary, an inverse correlation was detected between length of treatment and bone mineral density z-scores. Treated patients showed a significantly higher concentration of serum alkaline phosphatase, osteocalcin, urinary calcium/creatinine and hydroxyproline/creatinine in comparison with the controls. CONCLUSIONS: Our study suggests that thyroxine replacement therapy in patients with suppressed thyroid stimulating hormone levels increases postmenopausal bone loss.

[Effects of ipriflavone on bone loss induced by GnRH analog]. / Effetti dell'ipriflavone sulla perdita ossea indotta da un analogo del GnRH.

The aim of this study is to evaluate the association between GnRH analogues and ipriflavone, drug modulating the bone turnover limiting the negative bone effects of analogue. Thirty patients (33 +/- 5.4 years, mean +/- SD) affect by benign gynecological conditions in which there was an indication to use GnRH analogs have been treated with leuprolide acetate at the monthly intramuscular dose of 3.75 mg, for six months. Fifteen of these patients also received 600 mg/day per os of ipriflavone (group A), while the other 15 patients have been treated exclusively with leuprolide acetate (group B). Before and after treatment, radial bone mineral density (BMD) and main markers of bone turnover were measured in all patients. Before treatment no difference in the considered parameters could be detected between the two groups. In group A, after 6 months of treatment no significant decrease in BMD and no variations in the bone turnover parameters. On the contrary, in group B, after six months of treatment, a significant decrease (p < 0.05) in BMD was observed in comparison to basal and group A values. In the same group alkaline phosphatase, osteocalcin and urinary calcium/creatinine and hydroxyproline/creatinine ratio proved significantly increased in comparison to basal and group A values (both with p < 0.05). Ipriflavone, therefore, seems to be effective in counteracting the negative effects of GnRH-a induced on bone.

Effects of alendronate on bone loss in pre- and postmenopausal hyperthyroid women treated with methimazole.

High levels of thyroid hormones accelerate bone turnover. The aim of the present study was to evaluate the effects of treatment with alendronate in patients affected by hyperthyroidism and osteoporosis. We studied 40 hyperthyroid patients with bone loss, divided into two groups according to menopausal state. Before treatment and after 6 and 12 months, serum thyroid hormones levels, serum osteocalcin level and bone mineral density were evaluated. In all patients we observed an increase in bone mineral density after treatment with alendronate, and a corresponding decrease in serum osteocalcin level.

Changes in bone mineral density and calcium metabolism in breastfeeding women: a one year follow-up study.

The aim of this study was to evaluate bone metabolism in breast-feeding women. Thirty-six healthy women (24-31 yr, mean age 28.1 +/- 1.8 yr) were divided into 2 groups: group A including 18 women that exclusively breast-fed for 6 months, and group B composed of 18 women in whom lactation was inhibited with bromocriptine. Three days and 3, 6, and 12 months after delivery, distal radius, and lumbar spine bone mineral density (BMD) and some of the main biochemical parameters of bone turnover were assessed. In group A, we detected a significant decrease (P < 0.01 vs. basal and group B) in lumbar spine and distal radium BMD during breast-feeding. An incomplete recovery of BMD was detected 6 months after breast-feeding interruption. In group B, no significant changes occurred in BMD. In group A, during lactation, serum osteocalcin and urinary hydroxyproline showed a significant increase (P < 0.01 vs. basal and group B), while parathyroid hormone was significantly decreased (P < 0.02 vs. basal and group B). No significant variations in these parameters occurred in group B throughout the study. Our findings show that a significant decrease of BMD occurs during lactation and that this decrease is only partially recovered 6 months after interrupting breast-feeding.

Heterotopic pregnancy in a woman without previous ovarian hyperstimulation: ultrasound diagnosis and management.

Heterotopic pregnancy (HT) in the absence of a previous ovarian hyperstimulation is a very rare condition. Transvaginal ultrasonography (TV) in the case of first trimester pelvic pain allows a high diagnostic reliability in the identification of HT and a successful conservative treatment by means of TV potassium chloride injection.

Observations on the use of purified follicle-stimulating hormone in the treatment of luteal phase defects.

We treated 18 infertile patients affected by histologically confirmed luteal phase deficiency with 75 IU of purified follicle-stimulating hormone (FSH) daily during the first 5 days of the cycle. Patients who were not pregnant after the first cycle of treatment underwent a second cycle. In the second cycle the daily doses of purified FSH were doubled if luteal phase deficiency had persisted during the first cycle. During the two cycles before treatment and during treatment, patients underwent an endometrial biopsy 1-3 days before the expected onset of menses. An assessment of progesterone serum concentrations was also performed on days 8, 6 and 4 before the expected onset of menses. Treatment was administered in a total of 33 cycles resulting in 30 ovulatory cycles. Six pregnancies were achieved. Among non-conception ovulatory cycles, 13 presented delayed endometrial dating and 11 normal endometrium. The mean +/- SD of the sum of the three progesterone determinations was 14.7 +/- 1.4 ng/ml in pretreatment cycles, 14.6 +/- 1.6 ng/ml in cycles with normalization of endometrial dating, 14.8 +/- 1.7 ng/ml in cycles with persistence of luteal phase deficiency and 30.4 +/- 3.0 ng/ml in conception cycles (P < 0.05 versus other groups). We conclude that purified FSH, if effective in the treatment of luteal phase deficiency, does not act through an increase in progesterone concentrations.

Endometrial hyperplasia: efficacy of a new treatment with a vaginal cream containing natural micronized progesterone.

Seventy-eight premenopausal women affected by benign endometrial hyperplasia (60 simple and 18 complex) were treated from the 10th to the 25th day of the menstrual cycle with a vaginal cream containing 100 mg of natural micronized progesterone in polyethylene glycol base. The treatment lasted 3 months in 58 patients and 6 in the other 16 patients. Four patients were lost from the study. We observed a total of 67 complete regressions (90.5%) of which 58 (78.3%) occurred in the first 3 months and 9 (11.5%) after 6 months of treatment. Simple hyperplasia showed a significantly higher response to treatment in comparison with the complex type (P < 0.001). The most frequent endometrial pattern detected in the patients in whom hyperplasia regressed was of a secretive type. Recurrence of hyperplasia occurred in 1 out of 58 (1.72%) patients at the 3rd month and in 3 out of 49 (6.1%) patients at the 6th month after treatment. There were no significant differences between the two hystological groups in the percentage of recurrence. During treatment we observed a significant reduction of the amount, duration and frequency of the menstrual bleeding. Minimal side-effects were observed. In conclusion, for its effectiveness and safety, vaginal administration of natural micronized progesterone seems to be an interesting approach to benign endometrial hyperplasia, particularly indicated in women also affected by metabolic disorders.

Efficacy, cycle control and side-effects of two monophasic combination oral contraceptives: gestodene/ethinylestradiol and norgestimate/ethinylestradiol.

Two monophasic oral contraceptives containing gestodene (GTD, 75 micrograms) and ethinylestradiol (EE, 30 micrograms) or norgestimate (NGS, 250 micrograms) and EE (35 micrograms) were compared during the first six cycles of use. The subjects were randomly assigned to receive either type: 97 received GTD/EE and 92 NGS/EE. Six women in the GTD/EE group and nine in the NGS/EE group withdrew from the study; three (3%) and two (2%), respectively, withdrew because of adverse reactions. A total of 562 cycles for GTD/EE and 523 for NGS/EE were available. No woman became pregnant during the study. Overall, 94.4% of cycles in the GTD/EE group and 92.8% in the NGS/EE group were normal. A similar incidence of breakthrough bleeding (0.2% of cycles for GTD and 1.6% for NGS) and spotting (5.4% vs. 5.6%) was observed. Amenorrhea was never reported. Duration of withdrawal bleeding tended to be slightly longer in the NGS/EE group, significantly so for cycles 2 (0.5 days, p = 0.016), 4 (0.5 days, p = 0.031) and 5 (0.4 days, p = 0.045). Cycle 2 was significantly longer in the GTD/EE group (0.3 days, p = 0.027). Side-effects were reported by 12 (12%) women in the GTD/EE group and 13 (14%) in the NGS/EE group. The most common side-effects were headache (five cases (5%) in the GTD/EE group and two (2%) in the NGS/EE group) and breast pain (three (3%) and eight (9%) cases respectively). There were no statistically significant differences between the two groups with respect to change in body weight or changes in blood pressure and in laboratory data.(ABSTRACT TRUNCATED AT 250 WORDS)

A new fluoride preparation for the prevention of postmenopausal osteoporosis: calcium monofluorophosphate.

Fifty-six postmenopausal women aged 52.4 +/- 6.7 years (SD) were treated for 12 months with L-glutamine calcium monofluorophosphate. Each patient received four tablets/day, providing a total dose of 20 mg of fluoride and 600 mg of elemental calcium. Bone mineral density was measured at baseline and after 6 and 12 months of treatment by dual photon absorptiometry of the distal forearm. At these times, serum levels of alkaline phosphatase and osteocalcin, and urinary concentrations of hydroxyproline and calcium, were also assayed. Results were compared with a control group of 50 untreated postmenopausal women with similar clinical characteristics. Forty-nine patients completed the study. Bone mineral density in the treated patients showed a significant increase after 6 months in comparison with both baseline (p < 0.01) and controls (p < 0.01). After 12 months no significant further increase in bone mineral density was detected. In the control group, a significant decrease of bone mineral density was observed at this time (p < 0.01). After 6 months, serum osteocalcin levels were significantly increased in the treated group (p < 0.01 vs. basal and controls). The other biochemical parameters did not show any significant variations. After 12 months, all the biochemical parameters evaluated, with the exception of serum alkaline phosphatase, were significantly different in comparison with the control group (p < 0.01). Osteocalcin levels also increased in comparison with the basal value (p < 0.01). Adverse effects were mild. However, seven patients stopped the treatment before the 6th month because of gastrointestinal complaints.(ABSTRACT TRUNCATED AT 250 WORDS)